This invention relates to solid oral preparations containing active urea hydrogen peroxide, i.e. UHP without glycerol. The term "oral preparations" comprises solid products which in the ordinary course of usage are retained in the oral cavity for a time sufficient to release urea and hydrogen peroxide in a form to effectively neutralize acids formed in bacterial agglomerates on teeth (dental plaque) and in periodontal niches.
Acids are formed in dental plaque subsequent to eating or drinking fermentable carbohydrates such as sugar in foods, beverages, snacks, desserts, sweets, confectionery, etc. Sugars, especially white refined sugar (sucrose) are known to initiate and promote dental caries especially when consumed frequently between meals. It is generally acknowledged in the field that acids formed in dental plaque from sugars (hexoses, pentoses, aldoses, ketoses) will demineralize the tooth surface and produce cavities. Acid formation in plaque occurs within a few minutes after the consumption of sugar containing food or sweets. Data have been presented by Imfeld, Th.: Proceedings of the ERGOB Conference on Health and Sugar Substitutes, Geneva, 1978, S. Karger, Basel p. 218: Subsequent to exposure to sucrose, plaque acidity 100 times higher than before exposure is recorded within 5 minutes. Hydrogen ion concentrations almost 1000 times greater are attained in 10 minutes.
Alkaline compounds, for example sodium carbonate, sodium bicarbonate, ammonium phosphates and similar ones have been suggested in the art to neutralize plaque acids in order to inhibit the cariogenic potential of dietary fermentable carbohydrates. The soapy taste of alkaline buffers has hindered their general acceptance and in addition their acid neutalizing power fades rapidly because of dilution by saliva.
Ammonium phosphate- and urea-containing dentifrices were available on the American and European markets in the fifties with claims of anticaries properties according to Cohen, A., Donzanti, A.: JADA 49: 185, 1954, which later, however, could not be confirmed, probably because of the temporal dissociation between use of dentifrice and carbohydrate consumption. Toothbrushing with toothpaste is in general, not performed immediately after meals and is usually not performed at all after consumption of snacks. The English authors Clark, R., Hay, D. I., Schram, C. J., Wagg, B. J.: Brit. D. J. 111: 244, 1961 and Gilders, B. T.: Brit. D. J. 110:17, 1961, recommended the use of sour "dental cleaning tablets" stimulating a copious flow of natural saliva. Neutralization of a sugar exposed plaque was inadequate because of the acid content of the cleaning tablets.
Liquids or gels with urea hydrogen peroxide (UHP) in general hitherto have been shown to be beneficial in treating inflammatory oral disease, such as chronic gingivitis by Pomerance, A. S., Tanchester, D.: JADA 66: 67, 1963; Rundegren, J. Fornell, J., Ericson, T.: Scand. J. dent. Res. 81:543, 1973; Kaslick, R. S., Shapiro, W. B., Chasens, A. I.: J. Periodontol. 46: 230, 1975 and Zinner, D. D., Duany, L. F., Llorente, M.: J. Prev. Dent. 5: 38, 1978 and in healing of experimental wounds by Manhold, J. H., Weisenger, E., Rustogi, K.: J. Periodontal. 45: 312, 1974. All investigators agree that the anti-inflammatory effect is mainly the result of the antibacterial action of oxygen since hydrogen peroxide alone, or chemicals not containing urea but releasing oxygen (sodium perborate, sodium peroxyborate, zinc peroxide, monoxylchlorosene) also have anti-flammatory action.
Other investigators--Brown, E. A., Cruickshank, G. A.,: J. Dent. Res. 26: 83, 1947; Shipman, B., Cohen E., Kaslick, R. S.: J. Periodontol. 42: 283, 1971; Pomerance, A. S., Tanchester, D.: JADA 66: 67, 1963; Rundegren, J., Fornell, J., Ericson, T.: Scand. J. dent. Res. 81: 543, 1973; Zinner, D. D., Duany, L. F., Chilton, N. W.: Pharmacology and Therapeutics, 1: 7, 1970; Chaconas, S. J., Newman, M. G., Newman, S. L.: IADR Kopenhagen 56, 1977, Zinner, D. D., L. F., Llorente, M.: J. Prev. Dent. 5: 38, 1978--have shown UHP in glycerol containing solutions or gels to be effective in controlling the amount of mineralized or non-mineralized dental plaque.
The reduction of mouth odor, due to thiols (Tonzetich, J., Johnson, P. W.: Arch. oral Biol. 22: 125, 1977) by oxygenating chemicals has also been reported recently by Kaizu, T., Tsunoda, M. Sato, H., Sato, T: Bull. Tokyo dent. Coll. 19: 209, 1978.
None of the above mentioned publications, however, discloses the use of active UHP, i.e. UHP not solved or contained in glycerol, in a solid preparation for the neutralization of acids formed from fermentable carbohydrates in dental plaque, i.e. in the pharmaceutical treatment of caries.
Stephan, T. M.: J. dent. Res. 22: 63, 1943 reported that the pH of "thick bacterial growths" located in the cavities of preexisting dental caries lesions is lowered by a sugar rinse (glucose) and that the decreased pH can be raised and maintained at a higher level for up to 24 hours by one subsequent 4 minute rinse with a 50 percent urea solution which had to be followed by several water rinses to remove excess urea. Concentrations in the 10 to 16 percent urea level had a much lower alkalizing potential. The observations by Stephan did not, in the last 35 years, have any dental applicability. His observations differ from the present invention in several important aspects.
(1) Stephan's experiments used urea alone to inhibit acid formation of "thick bacterial growths" located in cavities of preexisting caries lesions. The present invention proposes to use UHP for the neutralization of acid induced in plaque growing on still intact teeth. In addition, the microbiological composition of bacterial growths in carious cavities is different from the microbiology of dental placque. Long lasting inhibition of pH drops after the 50 percent urea rinse reported by Stephan have not been confirmed by other investigators. Stephan's results are explainable by soaking of the bacteria filled cavities with 50 percent urea which is not possible on smooth, intact tooth surfaces with an overlying cover of plaque; urea in rinses is in this case cleared rapidly from the oral cavity.
(2) Urea is not stable when exposed to humidity nor is it stable at 50 percent concentrations and is easily transformed into an organoleptically unacceptable, injurious product. It is possible to formulate stable oral preparations with UHP.